Endothelial-constitutive nitric oxide synthase exists in airways and diesel exhaust particles inhibit the effect of nitric oxide

Abstract

Diesel exhaust particles (DEP) are an important cause of air pollution and are thought to be responsible for some respiratory ailments, but the exact mechanism is not known. We evaluated whether DEP inhibit nitric oxide (NO) synthesis in bronchi as NO is present in the exhaled air and has a physiological role in the respiratory tract. Aortic rings were also examined for comparison. We observed that acetylcholine (ACh) induced contraction of the bronchi was partially attenuated by the simultaneous release of NO. When bronchial rings were incubated either with N G-methyl-L-arginine (L-NMA): an inhibitor of NO synthase (NOS) or with DEP, the contraction to ACh was abolished. The source of the NOS was the bronchial epithelium and this endothelial-constitutive NOS was demonstrated by immunohistochemistry. DEP like L-NMA inhibited the ACh induced endothelium dependent relaxation in the aortic rings. The inhibition of NO release by DEP and L-NMA from bronchial and aortic rings was also confirmed by a selective NO electrode. We conclude that inhibition of NO availability by DEP may in part be responsible for the adverse respiratory effects seen by inhalation of these particles in polluted air.